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Expression of type III hyperlipoproteinemia in apolipoprotein E2 (Arg158→Cys) homozygotes is associated with hyperinsulinemia

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Author: Beer, F. de · Stalenhoef, A.F.H. · Hoogerbrugge, N. · Kastelein, J.J.P. · Leuven, J.A.G. · Duijn, C.M. van · Havekes, L.M. · Smelt, A.H.M.
Type:article
Date:2002
Institution: Gaubius Instituut TNO
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 2, 22, 294-299
Identifier: 236467
doi: doi:10.1161/hq0202.102919
Keywords: Adult · Age of Onset · Aging · Apolipoprotein E2 · Apolipoproteins E · Comorbidity · Coronary Disease · Estrogens · Female · Gene Expression · Gene Frequency · Homozygote · Humans · Hyperinsulinism · Hyperlipoproteinemia Type III · Male · Menopause · Middle Aged · Netherlands · Peripheral Vascular Diseases · Prevalence · Regression Analysis · Sex Factors

Abstract

Type III hyperlipoproteinemia (HLP) is mainly found in homozygous carriers of apolipoprotein E2 (apoE2, Arg158→Cys). Only a small percentage (<5%) of these apoE2 homozygotes develops hyperlipidemia, indicating that additional environmental and genetic factors contribute to the expression of type III HLP. In the present study, first, the prevalence of type III HLP among apoE2 homozygotes was estimated in a Dutch population sample of 8888 participants. Second, 68 normocholesterolemic and 162 hypercholesterolemic apoE2 homozygotes (type III HLP patients) were collected to investigate additional factors influencing type III HLP expression. In the Dutch population sample, apoE2 homozygosity occurred with a frequency of 0.6% (57 of 8888 individuals). Among the 57 E2/2 subjects, 10 type III HLP patients were identified (prevalence 18%). Comparison of normocholesterolemic E2/2 subjects and type III HLP patients showed that the latter had a significantly increased body mass index (25.6±4.0 versus 26.9±3.8 kg/m2, respectively; P=0.03) and prevalence of hyperinsulinemia (26% versus 63%, respectively; P<0.001). Multiple linear regression analysis demonstrated that most of the variability in type III HLP expression can be explained by fasting insulin levels (partial correlation coefficient ≈0.50, P<0.001). In contrast to men, apoE2 homozygous women aged ≥50 years had significantly higher plasma lipid levels than their counterparts aged <50 years. These data demonstrate that the expression of type III HLP in E2/2 subjects is elicited to a large extent by hyperinsulinemia. In addition, in female apoE2 homozygotes, the expression increases with age; this increase is most likely due to the loss of estrogen production. Chemicals/CAS: Apolipoprotein E2; Apolipoproteins E; Estrogens